Exploring differences in substance use behaviours among gender minority and non-gender minority youth: a cross-sectional analysis of the COMPASS study

Abstract Introduction: Research characterizing substance use disparities between gender minority youth (GMY) and non-GMY (i.e. girls and boys) is limited. The aim of this study was to examine the differences in substance use behaviours among gender identity (GI) groups and identify associated risk and protective factors. Methods: Cross-sectional data from Canadian secondary school students (n=42107) that participated in Year 8 (2019/20) or Year 9 (2020/21) of the COMPASS study were used. Hierarchal logistic regression models estimated current substance use (cigarettes, e-cigarettes, binge drinking, cannabis and nonmedical prescription opioids [NMPOs]). Predictor variables included sociodemographics, other substances, mental health outcomes, school connectedness, bullying and happy home life. Interaction terms were used to test mental health measures as moderators in the association between GI and substance use. Results: Compared to non-GMY, GMY reported a higher prevalence for all substance use outcomes. In the adjusted analyses, GMY had higher odds of cigarette, cannabis and NMPO use and lower odds for e-cigarette use relative to non-GMY. The likelihood of using any given substance was higher among individuals who were involved with other substances. School connectedness and happy home life had a protective effect for all substances except binge drinking. Bullying victimization was associated with greater odds of cigarette, e-cigarette use and NMPOs. Significant interactions between GI and all mental health measures were detected. Conclusion: Findings highlight the importance of collecting a GI measure in youth population surveys and prioritizing GMY in substance use–related prevention, treatment and harm reduction programs. Future studies should investigate the effects of GI status on substance use onset and progression among Canadian adolescents over time.

• Gender minority youth (GMY) were more likely to use cigarettes, cannabis and nonmedical prescription opioids and less likely to use e-cigarettes than girls and boys.• GMY experiencing symptoms of depression or anxiety were less likely to binge drink than GMY without symptoms.• GMY experiencing symptoms of anxiety were more likely to use nonmedical prescription opioids than GMY without symptoms.• These findings support the need to prioritize GMY in substance use prevention programs.• Youth surveillance studies should adopt the two-step gender identity measure.

Introduction
Adolescence is a unique time in which individuals between the ages of 10 and 19 develop their gender identity (GI) and sexual orientation. 1 According to the Survey of Safety in Public and Private Spaces, in 2018, individuals aged 15 to 24 years accounted for 30% of the lesbian, gay, bisexual, transgender, queer and Two-spirited (LGBTQ2+) population in Canada, as opposed to 14% of the non-LGBTQ2+ (i.e. an Indigenous person whose GI has both male and female spirits) populations. 3 date, GMY have been understudied in substance use research, as studies typically focus on the differences between cisgender boys and girls. 3,4This is because questions about GI have not yet been standardized on large-scale populationbased surveys, thereby limiting the accuracy and inclusiveness of the data collected and mischaracterizing health and behavioural outcomes for GMY. 3,5Furthermore, many studies focussing on GMY are generally small-scale, lack comparison groups or fail to recognize that sexual orientation, SAB and GI are conceptually different. 3,5,6owever, this is slowly changing, with national surveys adopting the two-step measure (Step 1 asks SAB; Step 2 asks current GI), as well as researchers, funders and journal editors emphasizing the need to examine the impacts of both sex and gender on health outcomes. 3,7][10][11][12] In 2017, findings from a crosssectional study revealed that nonbinary Canadian youth (Grades 9-12) were 2.26 times more likely to ever use cannabis than males. 13A cross-sectional analysis of a sample of California youth (Grades 7-12) found that transgender youth had higher rates of lifetime, current and in-school substance use compared to non-transgender peers. 8Similarly, a national survey in the US highlighted that the rates of lifetime alcohol and past-30-day cigarette and cannabis use were higher among transgender youth than cisgender peers. 10Emerging evidence also anticipates GMY may have been disproportionately affected by the COVID-19 pandemic, thereby further exacerbating their risk for using substances. 14bstance use disparities among GMY may be explained by the minority stress theory, which postulates that GMY use substances to cope with the unique social stressors they experience in schools, families and communities as a result of their marginalized or stigmatized identities. 4,15,16he chronic stressors that impact their health and well-being may be external (distal) objective stressors (e.g.discrimination), proximal subjective stressors (e.g.hiding one's GI), or both. 15The risk for problematic substance use may be further heightened among GMY who, in the absence of social support (e.g.[17] Currently, the majority of research investigating GMY's substance use behaviours stems from the US. 9,10,12,15Given the similar experiences with minority stressors, we expect Canadian GMY's substance use patterns to mirror those in the US. 4 Understanding substance use behaviours among Canadian GMY is critical in preventing adverse health and social outcomes and informing interventions efforts to effectively support the unique needs of this population.Thus, given the limited large-scale research among Canadian youth (aged 12-18), 13,18 the purpose of this study was to (1) examine the differences in substance use behaviours between Canadian GMY and non-GMY, and (2) identify associated risk and protective factors.

Ethics approval
All procedures employed by the COMPASS study were approved by the University of Waterloo Office of Research Ethics (ORE #30118) and appropriate school board committees.

Procedure
The COMPASS study is a prospective cohort study that annually collects data from full school samples of Canadian secondary school students (Grades 9-12, Secondary I-V in Quebec). 19Schools that permit an active-information passive consent parental permission protocol, 20 which limits self-selection and response bias in substance use research, were purposefully sampled. 21A full description of the COMPASS study methods is available online (https:// uwaterloo.ca/compass-system/about).
Cross-sectional data from two consecutive waves (Year 8 [Y8]: 2019/20; Year 9 [Y9]: 2020/21) were used to increase the sample size among GMY.An anonymous, selfgenerated code was used to identity unique participants.Students were entered into the study once; for students that participated in both years, only their Y9 responses were used.Details on the data linkage process are described elsewhere. 22ata in Y8 were collected between September 2019 and February 2020 via the paper-based COMPASS Student Questionnaire, which was completed during class time. 23Since March 2020, when schools first suspended in-person learning due to COVID-19 restrictions, students have completed an online COMPASS Student Questionnaire 24 using Qualtrics XM 25 survey software.
Consistent with youth surveillance systems at the time of data collection, 5,26,27 the COMPASS student questionnaire in Y8 and Y9 measured students' GI with the question, "Are you female or male?" Response options included "female," "male," "I describe my gender in a different way" and "I prefer not to say (PNTS)."While the measure used enabled youth to identify with a GI outside the traditional binary categories, we recognize that by not specifying "sex" or "gender," this question does not differentiate between youths' SAB and current GI.Thus, the question could be construed as measuring students' GI or biological sex. 28,29wever, given that this study primarily focusses on the socially constructed roles, behaviours and identities of youth, we categorized students who responded "female" and "male" as "girl" and "boy," respectively, (i.e."non-GMY").Students who responded, "I describe my gender in a different way" were categorized as "GMY."We acknowledge that our definition of "non-GMY" does not meet the preferred cisgender classification.However, seeing that we do not have data for students' SAB, we cannot definitively categorize youth as "cisgender."Instead, we can utilize the existing gender measure to differentiate youth that do not self-identify with the conventional binary options from those that do, and provide further insight into the substance use disparities between groups-a topic on which there is a dearth of evidence.

Mental health
Self-reported past-week depression symptoms (e.g.negative affect, somatic symptoms and amotivation) were assessed using the 10-item Center for Epidemiologic Studies Depression Scale Revised (CESD-R-10). 30tudents responded to items using a 4-point Likert scale (0 = "none or < 1 day" to 3 = "5-7 days").Sum scores were dichotomized, whereby a score of ≥ 10 signified students had clinically relevant symptoms of depression (henceforth referred to as "depression"). 30The CESD-R-10 items had an internal consistency of α = 0.992.
The Generalized Anxiety Disorder 7-item (GAD-7) scale was used to measure selfreported symptoms of anxiety in the past two weeks. 31Students' self-perceived feelings of worry, fear and irritability were rated using a 4-point Likert scale (0 = "not at all" to 3 = "nearly every day").Sum scores were dichotomized, whereby a score ≥ 10 denoted students had clinically relevant anxiety symptomology (henceforth referred to as "anxiety"). 31Internal consistency of GAD-7 items was high (α = 0.991).a Final analytic sample.
b Combination: student receives money from multiple sources including their job, occasional work and/or parents.
Students' self-rated psychosocial well-being (e.g.psychosocial prosperity, optimism and relationships) was measured using the Flourishing Scale. 32Students responded to 8 items using a 5-point Likert scale (0 = "strongly disagree" to 4 = "strongly agree").Sum of the scores ranged from 8 to 40, where higher sum scores indicated greater well-being or flourishing.The Flourishing Scale had high internal consistency (α = 0.995).

Other covariates
Students were asked, "In the last 30 days, in what ways have you been bullied by other students?"Responses were dichotomized, with "yes" indicating having been bullied (e.g.physical attacks, verbal attacks, cyber-attacks, damage to or theft of possessions) and "no" indicating not having been bullied.
School connectedness was measured using an adapted version of the National Longitudinal Study of Adolescent Health 5-item scale, 37 which asks students to indicate how strongly they agree or disagree with the following five statements: "I feel close to people at my school," "I feel I am part of my school," "I am happy to be at my school," "I feel the teachers at my school treat me fairly" and "I feel safe in my school."A sixth item, "Getting good grades is important to me" was added.A sum score ranging from 6 to 24 was developed, with higher sum scores indicating greater feelings of connectedness.
On a 5-point Likert scale, students rated how much they agreed or disagreed with the statement "I have a happy home life."A response of 1 or 2 indicated students strongly agreed or agreed, respectively, that they had a happy home life.Compared to girls and boys, GMY had a higher prevalence of past-month use for all substances, with the use of cigarettes, cannabis and NMPOs being at least two to six times higher.Between girls and boys, the prevalence of substance use was similar.A substantially higher proportion of GMY, followed by girls, reported depression and anxiety compared to boys.On average, GMY reported lower mean flourishing and school connectedness scores and greater mean DERS scores than non-GMY.Boys had similar scores for flourishing and school connectedness as girls but had lower DERS scores.It should be noted that after GMY, students that did not disclose their gender status had the highest proportions of cigarette, cannabis and NMPO use and mental health and social problems.

Predicting substance use
Tables 3 and 4 present logistic regression results for cigarette use, e-cigarette use, binge drinking and cannabis use.Models I (unadjusted) and II (demographic-adjusted) indicate that GMY were more likely to engage in current substance use relative to non-GMY.After adjusting for concurrent substance use (Model III), cigarette, cannabis and NMPO use remained significant, with a positive association.
In the fully adjusted model (Model IV, which includes covariates), the adjusted odds ratio (aOR) was determined for each outcome.GMY had higher odds of using cigarettes (aOR GMYvs.Boys = 1.61; aOR GMYvs.Girls = 1.95), cannabis (aOR GMYvs.Boys = 1.39; aOR GMYvs.Girls = 1.81) and NMPOs (aOR GMYvs.Boys = 1.76; aOR GMYvs.Girls = 1.94) and lower odds of using e-cigarettes (aOR GMYvs.Boys = 0.78; aOR GMYvs.Girls = 0.72) than non-GMY peers.Girls had a lower likelihood of cigarette use (aOR = 0.83), binge drinking (aOR = 0.83) and cannabis use (aOR = 0.77) compared to boys.Youth who used any of the substances were significantly more likely to use other substances.Prior to testing for interaction effects between mental health predictors and gender, youth with depression were 10% to 36% more likely to binge drink and use e-cigarettes, cannabis and NMPOs than those without depression.Anxiety had no significant effect on substance use.
Although flourishing was associated with all substances (except cannabis) and DERS was related to every substance except cigarettes, the magnitude of the associations was small.
School connectedness and happy home life were negatively associated with all substances except binge drinking.Students, on average, were 3% to 6% less likely to engage in substance use for every 1-point increase in school connectedness and 24% to 29% less likely if they reported having a happy home life.Youth who reported past-month bullying victimization had higher odds of using cigarettes (aOR = 1.20), e-cigarettes (aOR = 1.44) and NMPOs (aOR = 1.73).

Moderating effects of mental health predictors
Overall, regardless of depression and anxiety status, a greater percentage of GMY compared to girls and boys reported e-cigarette use, binge drinking and NMPOU (Figure 1a-e).Depression was found to significantly moderate the association between gender and e-cigarette use and between gender and binge drinking.GMY with depression (22.3%) had a significantly lower prevalence of binge drinking compared to those without depression (34.2%, p < 0.001; Figure 1c].Comparatively, the prevalence of e-cigarette use and binge drinking was significantly higher for girls with depression than without (p < 0.001; Figure 1a, c).
Two-way interaction effects between gender and anxiety existed in e-cigarette use, binge drinking and NMPOU.GMY without anxiety had a significantly higher prevalence of binge drinking (29.9%) than GMY with anxiety (22.3%, p = 0.005; Figure 1d).The proportion of girls and boys with anxiety using e-cigarettes was significantly higher compared to girls and boys without anxiety (p < 0.05; Figure 1b).NMPOU was greater among GMY with anxiety (19.2%) than GMY without anxiety (7.2%; p = 0.005; Figure 1e].Boys with anxiety engaged in more NMPOU (8.2%) than boys without anxiety (2.9%; p = 0.008; Figure 1e).Interaction effects between gender and flourishing and gender and DERS were significant for all outcomes except cigarette use.However, the estimates of the observed associations were small.Table 5 presents the two-way interaction effects.

Discussion
As expected from recent population studies surveying adolescents, [8][9][10][11]18,39 the prevalence of substance use was higher among GMY than girls and boys. Interstingly, the frequency of substance use was also significantly higher among youth that indicated "PNTS" than girls or boys.It is possible that substance use among youth that reported PNTS may be driven by their own unique set of challenges (e.g.unsure about their GI).
Our results were consistent with De Pedro and colleagues' cross-sectional study, 9 which revealed higher rates of past-30-day cigarette and cannabis use among transgender youth compared to non-transgender peers.When adjusting for only sociodemographic characteristics, we found GMY had a higher likelihood of current e-cigarette use and binge drinking, similar to existing research. 9,39,40However, in our fully adjusted models, we found GMY relative to non-GMY had a lower likelihood of current e-cigarette use and that GMY status alone did not significantly predict current binge drinking.Our unique findings may be explained by the additional covariates (i.e.other substances, mental health outcomes, school connectedness, bullying victimization and happy home life) in our model and the relatively small difference in prevalence estimates between gender groups for e-cigarette use and binge drinking compared to the larger discrepancy seen for other substances.Consistent with previous findings, we found that a greater proportion of GMY, followed by girls, reported mental health issues compared to boys. 8,41,42Interaction analyses indicated that the associations between gender and e-cigarette use, gender and binge drinking, and gender and NMPOU varied depending on mental health status.As expected, the frequency of NMPOU was greater among youth with clinically relevant anxiety symptoms than those without. 4,43Although GMY reported higher e-cigarette use and binge drinking compared to non-GMY, we found that binge drinking was lower among GMY with clinically relevant depression and anxiety symptoms than GMY without these conditions.This contradicts the current literature that suggests GMY experiencing internalizing symptoms will engage in greater substance use.a All two-way interaction effects were tested individually in separate models.
b Final analytic sample: all models adjusted for school year, sociodemographics, substance use, mental health and other covariates (bullying victimization, school connectedness and happy home life).
c The interaction effect on the likelihood of substance use was assessed within each gender identity group (i.e. with or without depression or anxiety) as anxiety and depression are categorical variables.
d The interaction effect on the likelihood of substance use was assessed across gender identity groups as flourishing and emotional dysregulation are continuous variables.
* p < 0.05 did not differ among GMY based on mental health status.However, for girls and boys, clinically relevant internalizing symptoms were associated with greater e-cigarette use, binge drinking and NMPOU.
Additionally, and contrary to expectations, 16,44 we did not find greater psychological wellbeing or poor emotional regulation skills to influence substance use among GMY.The insignificant findings may be because data were collected during the COVID-19 pandemic.The pandemic-induced lockdowns and restrictions, which upended youths' daily routines, could have driven deteriorations in mental health and emotional dysregulation among all participating youth, regardless of their GI. 45plausible explanation for our contradictory findings for binge drinking may be that GMY with internalizing symptoms are isolating themselves from social activities, in which binge drinking is common. 18or two-Spirit, lesbian, gay, bisexual, transgender, queer, intersex, and additional people who identify as part of sexual and gender diverse communities (2SLGBTQI+) youth, disclosing one's sexual or gender identity has been linked to lower selfesteem, which is a prospective risk factor for depression and anxiety. 46,47If "coming out" is a positive experience, one in which youth feel accepted and supported by family, friends and community members, GMY may experience greater self-esteem and fewer internalizing symptoms, allowing them to better connect and socialize with peers. 18,46,47Future GMY-based research is needed to better understand the relationship between minority stress factors, mental health and substance use.
This study, in line with existing research, 15,17 also highlights that among the entire study sample, perceived happy home life and school connectedness had a protective effect against substance use, while bullying victimization was associated with an increased risk.Future work should examine the mechanisms underlying the association between social health factors and substance use among GMY.

Strengths and limitations
A primary strength of this study is that it is the first to use a large sample of Canadian secondary school students to examine differences in current substance use behaviours between GMY and non-GMY.The large sample size of youth is achieved via the robust COMPASS data collection procedures and data linkage process.Additionally, the GI measure was able to successfully capture GMY.
Regarding the limitations of our study, first, our gender question does not identify the different subcategories of GMY (e.g.transgender, nonbinary).However, the proportion of GMY identified in our study (2%) aligns with other studies that sample youth attending secondary schools 48 and is slightly higher compared to population-based studies that focus solely on transgender youth. 39Second, purposive sampling was used to recruit schools and collect data, which may limit the generalizability to school-aged youth in Canada.Third, the use of self-report measures (e.g.GI, substance use) may have led to underreporting due to social desirability bias.However, these risks were mitigated with the use of an anonymous, active-information, passiveconsent data collection procedure that encourages participation as well as honest self-reporting. 20,21Fourth, the cross-sectional nature prohibits causal inferences.

Conclusion
We found significant disparities in substance use by GI, with GMY at a significantly greater risk of using some substances (i.e.cigarettes, e-cigarettes and NMPOs) compared to girls and boys.This study highlights the importance of adopting the two-step GI measure in population-based surveillance studies.Future studies should identify the longitudinal patterns of substance use behaviours by gender and sexual orientation status among Canadian adolescents.Such knowledge will be useful when implementing tailored community and school-based interventions that address the unique needs and challenges of GMY.

FIGURE 1 2
FIGURE 1The percentage of youth reporting current e-cigarette use, binge drinking and nonmedical prescription opioid use (NMPOU) as a function of (1) gender × depression and (2) gender × anxiety

TABLE 1 Chi-square analysis of demographic characteristics comparing students participating in Year 8 (2019/20) or Year 9 (2020/21) of the COMPASS study with missing outcome data versus complete data (N = 59 897) Student-level variable
Abbreviation: df, degrees of freedom.

TABLE 2 Characteristics of high school students (N = 42 107; 139 schools) participating in Year 8 (2019/20) or Year 9 (2020/21) of the COMPASS study, by gender identity status Student-level variable Gender identity a
Abbreviations: GMY, gender minority youth; NMPOU, nonmedical prescription opioid use; PNTS, prefer not to say; SD, standard deviation; Y8, Year 8; Y9, Year 9. a Complete case analysis.b All χ 2 and F tests were significant at p < 0.001.c Combination: student receives money from multiple sources including their job, occasional work and/or parents.

TABLE 3 Generalized estimated equation models predicting the likelihood of substance use outcomes among high school students participating in Year 8 (2019/20) or Year 9 (2020/21) of the COMPASS study (N = 41 537) Current cigarette use Current e-cigarette use Current binge drinking Current cannabis use Past-year NMPOU Model I a -ORs (95% CI)
Abbreviations: aOR, adjusted odds ratio; CI, confidence interval; GMY, gender minority youth; NMPOU, nonmedical prescription opioid use; OR, odds ratio; ref., reference group.a Model I is unadjusted.b Model II adjusts for school year and sociodemographic variables.c Model III adjusts for school year, sociodemographic and substance use variables.*p < 0.05

TABLE 4 Generalized estimating equation models predicting the likelihood of current substance use among high school students participating in Year 8 (2019/20) or Year 9 (2020/21) of the COMPASS study (N = 41 537)
Model IV adjusts for school year, sociodemographics, substance use, mental health and other covariates (bullying victimization, school connectedness and happy home life). a Figures (a)and (c) depict depression moderating the association between gender and e-cigarette use and gender and binge drinking, respectively.Figures (b), (d) and (e) depict anxiety moderating the association between gender and e-cigarette use, gender and binge drinking, and gender and NMPOU, respectively.
1,8E-cigarette useNotes:a Significant differences within each gender group with or without depression or anxiety.

TABLE 5 Generalized estimating equation models testing the moderating effects of mental health predictors on the relationship between gender identity status and substance use outcomes among a sample of high school students participating in Year 8 (2019/20) or Year 9 (2020/21) of the COMPASS study (N = 41 537)
Abbreviations: aOR, adjusted odds ratio; CI, confidence interval; GMY, gender minority youth; NMPOU, nonmedical prescription opioid use.